@article{06c1ea7d86b54c15ace3083cccbb7fd2,
title = "Canonical and atypical E2Fs regulate the mammalian endocycle",
abstract = "The endocycle is a variant cell cycle consisting of successive DNA synthesis and gap phases that yield highly polyploid cells. Although essential for metazoan development, relatively little is known about its control or physiologic role in mammals. Using lineage-specific cre mice we identified two opposing arms of the E2F program, one driven by canonical transcription activation (E2F1, E2F2 and E2F3) and the other by atypical repression (E2F7 and E2F8), that converge on the regulation of endocycles in vivo. Ablation of canonical activators in the two endocycling tissues of mammals, trophoblast giant cells in the placenta and hepatocytes in the liver, augmented genome ploidy, whereas ablation of atypical repressors diminished ploidy. These two antagonistic arms coordinate the expression of a unique G2/M transcriptional program that is critical for mitosis, karyokinesis and cytokinesis. These results provide in vivo evidence for a direct role of E2F family members in regulating non-traditional cell cycles in mammals.",
author = "Chen, {Hui Zi} and Ouseph, {Madhu M.} and Jing Li and Thierry P{\'e}cot and Veda Chokshi and Lindsey Kent and Sooin Bae and Morgan Byrne and Camille Duran and Grant Comstock and Prashant Trikha and Markus Mair and Shantibhusan Senapati and Martin, {Chelsea K.} and Sagar Gandhi and Nicholas Wilson and Bin Liu and Huang, {Yi Wen} and Thompson, {John C.} and Sundaresan Raman and Shantanu Singh and Marcelo Leone and Raghu Machiraju and Kun Huang and Xiaokui Mo and Soledad Fernandez and Ilona Kalaszczynska and Wolgemuth, {Debra J.} and Piotr Sicinski and Tim Huang and Victor Jin and Gustavo Leone",
note = "Funding Information: We thank L. Rawahneh, J. Moffitt and N. Lovett for excellent technical assistance with histology, and P. Wenzel for generating and collecting 123tko placentae. We also thank these individuals from OSUCCC Shared Resources: T. Wise, J. Palatini, H. Alders, P. Yan, P. Fada and B. Rodriguez (Microarray and Nucleic Acid Shared Resources); B. McElwain (Analytic Cytometry); R. Burry, K. Wolken, and B. Kemmenoe (Microscopy and Imaging); and K. La Perle (Comparative Pathology and Mouse Phenotyping). We are grateful for PL-1 antibodies provided by F. Talamantes (University of California, Santa Cruz, CA), Rcho-1 trophoblast stem cells from M. J. Soares (University of Kansas Medical Center, Kansas City, KS) and HepG2 cells from S. Jacobs. This work was funded by NIH grants to G.L. (R01CA85619, R01CA82259, R01HD047470, P01CA097189) and P.S. (R01CA132740). G.L. is a recipient of The Pew Charitable Trust Scholar Award and the Leukemia & Lymphoma Society Scholar Award. H-Z.C., M.M., S.S., S.R. and T. P. are recipients of the Pelotonia Fellowship Award.",
year = "2012",
month = nov,
doi = "10.1038/ncb2595",
language = "English (US)",
volume = "14",
pages = "1192--1202",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "11",
}